The H-2 major histocompatibility complex of the mouse controls a variety of traits which are important to research on transplantation, viral oncogenesis, disease resistance, and fundamental genetic and immunologic mechanisms. In this context it is also an important model for the HL-A complex in man. The broad, long-range objective of the proposed research is the elucidation of the number, organization, function and regulation of the multiple genes of the H-2 complex which control these diverse traits, especially the genes of the I region which control specific immune responses, T cell- B cell cooperation, the mixed leucocyte reaction (MLR), and the Ia lymphocyte antigens. Two general areas of approach are proposed: 1) Genetic organization-- Large scale screening for recombination and mutation within the complex will be undertaken. All H-2 variants will be extensively characterized for H-2-associated traits, in order to separate, identify and map the controlling genes. Particular attention will be given to analysis of I region traits. A computer program will be developed to assist the mapping analysis. 2) Genetic function-- To elucidate the functions of certain specific genes, more intensive studies will be done on selected traits. The Ss proteins will be analyzed for their biochemical properties, hormonal regulation, and relationship to the complement system. The relationship of Ia antigens to other I region traits will be probed by analyses of capacity of anti-Ia sera to inhibit these traits. Certain H-2 transplantation antigens will be further analyzed biochemically and serologically. A search for additional serological systems in the H-2 complex will also be made.